FAST-ACT: A phase II randomized double-blind trial of sequential erlotinib and chemotherapy as first-line treatment in patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC)

Lee, J. S.; Ignacio, Jorge; Yu, Chuan-Xin; Zhou, C.; Wu, Yi‐Long; Chen, Y.; Zhang, L.; Jin, Kaiqi; Johnston, Michael; Mok, Tony

doi:10.1200/jco.2008.26.15_suppl.8031

Cited by 20 publications

(13 citation statements)

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“…on d15-28 of 4-weekly chemotherapy cycles. Chemotherapy consisted of gemcitabine plus cisplatin or carboplatin for a maximum of 6 cycles (n = 154) with a subsequent erlotinib maintenance in patients showing clinical benefi t [9]. Response rate and PFS were in favour of the sequential erlotinib application (RR 37% vs. 24%, PFS: 7.2 vs. 5.5 months).…”

Section: Toll-like Receptor 9 (Tlr 9)mentioning

confidence: 97%

Non-small cell lung cancer

Dediu

Hilbe

2008

memo

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Non-small cell lung cancer 4/2008 ASCO Update -NSCLC 247 Th is congress report gives an overview of the most important news concerning lung cancer presented at ASCO 2008 meeting. Th e most interesting highlights were: (1) For the 1st-line treatment of patients with advanced NSCLC, Cetuximab, added to a platinum-based chemotherapy, sets a new standard and side eff ects (like acne-like rash) were as expected and manageable. (2) Insulin-like growth factor type I receptor (IGF-IR) in combination with chemotherapy could be an optimistic therapeutic option for NSCLC with squamous cell histology since fi rst results proved a response rate of 72% in this histological subtype. (3) Erlotinib as 1st-line treatment for elderly patients showed encouraging effi cacy. (4) For patients without progression after the fi rst line regimen, early introduction of a second line agent is an effi cient novel therapeutic option. Further validating studies are warranted.

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Section: Toll-like Receptor 9 (Tlr 9)mentioning

confidence: 97%

Non-small cell lung cancer

Dediu

Hilbe

2008

memo

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“…It is postulated that the erlotinib-and gefitinib-induced G 1 phase cell-cycle arrest may affect the efficacy of chemotherapy when administered simultaneously with EGFR TKIs. However, the role of erlotinib in combination with chemotherapy and as maintenance treatment was re-evaluated at the last ASCO meeting in 2008, with the presentation of a phase II randomized double-blind trial, named FASTACT (First-line Asian Sequential Tarceva plus Chemotherapy Trial) [25]. That trial tested a new combination strategy of erlotinib plus chemotherapy (erlotinib administered not concurrently with chemotherapy, but on days 15-28 of each chemotherapy cycle), which also represented a maintenance strategy because erlotinib was administered until progression.…”

Section: Molecularly Targeted Agentsmentioning

confidence: 99%

Potential Treatment Options After First-Line Chemotherapy for Advanced NSCLC: Maintenance Treatment or Early Second-Line?

et al. 2009

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Although substantial progress has been made in the therapeutic options currently available for patients with advanced non-small cell lung cancer (NSCLC), the overall survival profile remains poor for most patients. One of the strategies currently under investigation with the aim of prolonging survival in NSCLC patients is maintenance treatment with either a chemotherapeutic agent or a molecularly targeted agent after first-line chemotherapy. Moreover, this can consist of drugs included in the induction regimen or other noncrossresistant agents. With the currently available data, maintenance treatment with a different noncrossresistant agent (i.e., an early second-line treatment) is perhaps the most promising strategy. The drug chosen for the early second-line treatment should be a well-tolerated agent, considering that patients have just completed a particularly toxic platinum-based chemotherapy. Extending treatment with targeted agents rather than chemotherapy can provide longer progression-free and overall survival times without increasing toxicity. However, at the moment, only progression-free survival has been shown to be consistently superior with maintenance approaches; the evaluation of survival benefits is warranted before defining this strategy as a possible treatment option. Further studies are warranted to establish the role of maintenance chemotherapy in patients with advanced NSCLC.

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“…Erlotinib demonstrated significant improvement in overall survival in maintenance therapy. Responding pts continued to receive erlotinib or until disease progression or intolerable toxicity Primary endpoint was non-progression rate (= CR+PR+SD) Median number of treatment cycles received: 6 for chemo + erlotinib; 5 for chemo + placebo Statistically significant improvement in PFS (p=0.005) was observed in the erlotinib + chemotherapy arm Rash-like events: 66% in chemo + erlotinib arm; 35% in chemo + placebo arm Diarrhea: 24% chemo + erlotinib arm ; 18% in chemo + placebo arm Most common grade 3-5 adverse events (chemo + erlotinib vs. chemo + placebo): neutropenia (20% vs. 15%) anemia (8% vs. 6%) thrombocytopenia (5% vs. 5%) vomiting (3% vs. 8%) Overall safety profiles were similar between the two arms Key: AUC= area under concentration/time curve; CR=complete response; ECOG= Eastern Cooperative Oncology Group (ECOG); PFS= progression-free survival; PR=partial response; PS=performance status; Pts= patients; RR= response rate; SD = stable disease; TTP= time to disease progression A recent study [45] of intermittent TKI therapy with chemotherapy had suggested its preliminary efficacy but since the current standard of care still favors EGFR TKI for maintenance therapy, its role requires validation in long-term studies. Another study [46] from a single institution suggested that when patients with EGFR mutations progressed on erlotinib and when progression occurred in only a limited number of sites (<4), the same therapy or local disease control (e.g.…”

Section: Combination Of Tki Therapy With Chemotherapymentioning

confidence: 99%

Tyrosine Kinase Inhibitors for EGFR Gene Mutation-Positive Non-SmallCell Lung Cancers: An Update for Recent Advances in Therapeutics

Chung¹

2015

J Pharmacovigil

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The presence of activating gene mutations in the epidermal growth factor receptor (EGFR) of non-small cell lung cancer (NSCLC) patients is predictive (improved progression-free survival and improved response rate) when treated with small molecule tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib and afatinib. The two most common mutations that account for greater than 85% of all EGFR gene mutations, are in-frame deletions in exon 19 (LREA deletions) and point mutations in exon 21 (L858R). Exon 18 mutations occur much less frequently at about 4% of all EGFR gene mutations. Together, deletion19 and L858R gene mutations are present in about 10% of Caucasian patients and 20-40% of Asian patients with NSCLC. T790M gene mutation at exon 20 is associated with acquired resistance to EGFR TKIs. Early studies showed that activating EGFR gene mutations are most common in patients with adenocarcinoma histology, women, never smokers and those of Asian ethnicity. A recent multi-center phase III trial suggested that frontline EGFR TKI therapy with afatinib is associated with improved progressionfree survival compared to chemotherapy regardless of race. Moreover, guidelines suggest EGFR testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component), regardless of characteristics such as smoking status, gender, or race. The success of targeted therapies in NSCLC patients has changed the treatment paradigm in metastatic NSCLC. However, despite a durable response of greater than a year, resistance to EGFR TKIs inevitably occurs. This mini-review describes the clinically significant EGFR gene mutations and the efficacy of small molecule EGFR TKIs as targeted therapies for these gene mutations. Therapeutic strategies to overcome resistance, including selected emerging and novel therapies are discussed. Journal of PharmacovigilanceJou rn a l o f P harma c o v ig il a nc e

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FAST-ACT: A phase II randomized double-blind trial of sequential erlotinib and chemotherapy as first-line treatment in patients (pts) with stage IIIB/IV non-small cell lung cancer (NSCLC)

Cited by 20 publications

References 0 publications

Non-small cell lung cancer

Non-small cell lung cancer

Potential Treatment Options After First-Line Chemotherapy for Advanced NSCLC: Maintenance Treatment or Early Second-Line?

Tyrosine Kinase Inhibitors for EGFR Gene Mutation-Positive Non-SmallCell Lung Cancers: An Update for Recent Advances in Therapeutics

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